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Molecular Pathogenesis | Spotlight

The BB0345 Hypothetical Protein of Borrelia burgdorferi Is Essential for Mammalian Infection

Danielle E. Graham, Ashley M. Groshong, Clay D. Jackson-Litteken, Brendan P. Moore, Melissa J. Caimano, Jon S. Blevins
Guy H. Palmer, Editor
Danielle E. Graham
aDepartment of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Ashley M. Groshong
aDepartment of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
bDepartment of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA
cDepartment of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut, USA
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Clay D. Jackson-Litteken
aDepartment of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Brendan P. Moore
aDepartment of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Melissa J. Caimano
bDepartment of Medicine, University of Connecticut Health Center, Farmington, Connecticut, USA
cDepartment of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut, USA
dDepartment of Molecular Biology and Biophysics, University of Connecticut Health Center, Farmington, Connecticut, USA
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Jon S. Blevins
aDepartment of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
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Guy H. Palmer
Washington State University
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DOI: 10.1128/IAI.00472-20
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ABSTRACT

During the natural enzootic life cycle of Borrelia burgdorferi (also known as Borreliella burgdorferi), the bacteria must sense conditions within the vertebrate and arthropod and appropriately regulate expression of genes necessary to persist within these distinct environments. bb0345 of B. burgdorferi encodes a hypothetical protein of unknown function that is predicted to contain an N-terminal helix-turn-helix (HTH) domain. Because HTH domains can mediate protein-DNA interactions, we hypothesized that BB0345 might represent a previously unidentified borrelial transcriptional regulator with the ability to regulate events critical for the B. burgdorferi enzootic cycle. To study the role of BB0345 within mammals, we generated a bb0345 mutant and assessed its virulence potential in immunocompetent mice. The bb0345 mutant was able to initiate localized infection and disseminate to distal tissues but was cleared from all sites by 14 days postinfection. In vitro growth curve analyses revealed that the bb0345 mutant grew similar to wild-type bacteria in standard Barbour-Stoenner-Kelley II (BSK-II) medium; however, the mutant was not able to grow in dilute BSK-II medium or dialysis membrane chambers (DMCs) implanted in rats. Proteinase K accessibility assays and whole-cell partitioning indicated that BB0345 was intracellular and partially membrane associated. Comparison of protein production profiles between the wild-type parent and the bb0345 mutant revealed no major differences, suggesting BB0345 may not be a global transcriptional regulator. Taken together, these data show that BB0345 is essential for B. burgdorferi survival in the mammalian host, potentially by aiding the spirochete with a physiological function that is required by the bacterium during infection.

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The BB0345 Hypothetical Protein of Borrelia burgdorferi Is Essential for Mammalian Infection
Danielle E. Graham, Ashley M. Groshong, Clay D. Jackson-Litteken, Brendan P. Moore, Melissa J. Caimano, Jon S. Blevins
Infection and Immunity Nov 2020, 88 (12) e00472-20; DOI: 10.1128/IAI.00472-20

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The BB0345 Hypothetical Protein of Borrelia burgdorferi Is Essential for Mammalian Infection
Danielle E. Graham, Ashley M. Groshong, Clay D. Jackson-Litteken, Brendan P. Moore, Melissa J. Caimano, Jon S. Blevins
Infection and Immunity Nov 2020, 88 (12) e00472-20; DOI: 10.1128/IAI.00472-20
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KEYWORDS

Borrelia
Borrelia burgdorferi
Borreliella
Lyme disease
molecular genetics
pathogenesis
spirochetes

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